Xin-Yu Liu,1,* Wei Zhang,2,* Bao-Feng Ma,3 Mi-Mi Sun,4 Qing-Hua Shang2 

1College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250000, People’s Republic of China; 2Department of Liver Disease, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, Shandong, 250000, People’s Republic of China; 3The third department of encephalopathy, Jinan Integrated Traditional Chinese and Western Medicine Hospital, Jinan, Shandong, 271100, People’s Republic of China; 4Diagnosis and Treatment Center for Liver Diseases, Tai’an 88 Hospital, Tai’an, Shandong, 271000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Mi-Mi Sun; Qing-Hua Shang, Email mimysun@163.com; sq1713277397@163.com

Abstract: Hepatic fibrosis (HF) is a pathological process of structural and functional impairment of the liver and is a key component in the progression of chronic liver disease. There are no specific anti-hepatic fibrosis (anti-HF) drugs, and HF can only be improved or prevented by alleviating the cause. Autophagy of hepatic stellate cells (HSCs) is closely related to the development of HF. In recent years, traditional Chinese medicine (TCM) has achieved good therapeutic effects in the prevention and treatment of HF. Several active ingredients from TCM (AITCM) can regulate autophagy in HSCs to exert anti-HF effects through different pathways, but relevant reviews are lacking. This paper reviewed the research progress of AITCM regulating HSCs autophagy against HF, and also discussed the relationship between HSCs autophagy and HF, pointing out the problems and limitations of the current study, in order to provide references for the development of anti-HF drugs targeting HSCs autophagy in TCM. By reviewing the literature in PubMed, Web of Science, Embase, CNKI and other databases, we found that the relationship between autophagy of HSCs and HF is currently controversial. HSCs autophagy may promote HF by consuming lipid droplets (LDs) to provide energy for their activation. However, in contrast, inducing autophagy in HSCs can exert the anti-HF effect by stimulating their apoptosis or senescence, reducing type I collagen accumulation, inhibiting the extracellular vesicles release, degrading pro-fibrotic factors and other mechanisms. Some AITCM inhibit HSCs autophagy to resist HF, with the most promising direction being to target LDs. While, others induce HSCs autophagy to resist HF, with the most promising direction being to target HSCs apoptosis. Future research needs to focus on cell targeting research, autophagy targeting research and in vivo verification research, and to explore the reasons for the contradictory effects of HSCs autophagy on HF.

Keywords: hepatic fibrosis, HSCs autophagy, active ingredients of traditional Chinese medicine, HSCs activation